Tyrosine kinases are a family of proteins that catalyze phosphorylation of tyrosine residues in target proteins and play important roles in cellular signaling. Within this large family of proteins is the epidermal growth factor receptor (EGFR) family, which includes the receptor kinases ERBB1 (EGFR1, HER1), ERBB2 (c-Neu, HER2), ERBB3 (HER3), and ERBB4 (HER4). The ERBB kinases regulate a wide range of cellular responses, including cell proliferation, survival, migration and differentiation.
ERBB4 is a receptor tyrosine kinase member of approximately 180 kD. The interaction with its ligand promotes receptor dimerization and autophosphorylation, which leads to the regulation of several key pathways associated with cell proliferation, death and differentiation. Changes in ERBB4 activity through mutations and overexpression are associated with several types of cancers, psychiatric and cardiovascular disorders.
Currently, there are no drugs available for treating diseases that present through over activation of the ERBB4 pathway, such as breast cancer and lung cancer. Further, there are no methods of identifying patients which will be successfully treated with ERBB4 inhibitors, thereby preventing the treatment of patients exhibiting tumors inherently resistant to specific ERBB4 inhibitors.
There remains a great need for drugs that target diseases associated with over activation of the ERBB4 pathway, such as breast cancer and lung cancer, as well as methods of identifying patients likely to be successfully treated with ERBB4 inhibitors.